Rilpivirine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Rilpivirine: From HIV Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI), originally used to treat HIV infection and AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus infection, with 0 registered clinical trials and 5 publications (all preclinical or review) currently supporting this direction. This prediction mostly restates the drug's existing HIV use in an animal model, so it is not a true new human indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infectious disease; AIDS (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Rilpivirine is an NNRTI, a class of drugs that blocks the reverse transcriptase enzyme HIV-1 uses to copy its genetic material. Detailed mechanism of action data is not currently available in the compiled data, but this class mechanism is well established.
Simian immunodeficiency virus (SIV) and the chimeric SHIV/RT-SHIV used in macaque studies are the animal counterparts of HIV-1. RT-SHIV carries the HIV-1 reverse transcriptase, so it is a plausible target for rilpivirine. Macaque studies of long-acting rilpivirine, alone or with cabotegravir, report sustained virologic remission, a low frequency of drug-resistant variants and post-exposure prophylaxis activity.
These are animal-model data only. The prediction essentially describes the existing HIV indication in a preclinical model. No human trial supports it as a separate indication.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39632836 | 2024 | Preclinical (macaque SHIV) | Nature Communications | Oral emtricitabine/tenofovir alafenamide plus long-acting cabotegravir/rilpivirine in RT-SHIV-infected macaques, with or without an immune adjunct, aiming for remission |
| 26438501 | 2015 | Preclinical (macaque) | Antimicrob Agents Chemother | Long-acting rilpivirine selected drug-resistant variants at low frequency in SIV carrying HIV-1 RT |
| 41370971 | 2026 | Preclinical (PEP) | EBioMedicine | A single injection of long-acting cabotegravir plus rilpivirine evaluated as post-exposure prophylaxis in macaques |
| 42040962 | 2026 | Preclinical (macaque) | Research Square | Long-acting antiretroviral combinations in early-life SIV infection (the abstract centres on lenacapavir and cabotegravir) |
| 29746267 | 2018 | Review | Curr Opin HIV AIDS | Review of cabotegravir for antiretroviral therapy and prevention (indirect relevance) |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16568P | REKAMBYS Prolonged-Release Suspension for Injection 300mg/ml | Extended-release injectable suspension | Not stated in the licence record |
| SIN14363P | EDURANT Film-Coated Tablet 25 mg | Film-coated tablet | Not stated in the licence record |
| SIN16015P | ODEFSEY Film-Coated Tablet 200mg/25mg/25mg | Film-coated tablet | Not stated in the licence record |
Safety Considerations
- Contraindications suggested by the knowledge graph (not taken from label text): long QT syndrome (including familial), torsades de pointes, liver failure, liver disease, fatty liver disease, non-alcoholic steatohepatitis, kidney disease, Fanconi renotubular syndrome, chronic hepatitis B virus infection, lactic acidosis, hypophosphatemia, osteomalacia, rickets, gallbladder disease, obesity disorder and monogenic obesity. Some of these may relate to combination partners (such as tenofovir in Odefsey) rather than rilpivirine alone.
- Drug Interactions: 100 interactions were recorded. The listed ones include:
- Major: acid-reducing drugs (famotidine, ranitidine, cimetidine, omeprazole, esomeprazole, rabeprazole, dexlansoprazole), dexamethasone, dolasetron, cisapride.
- Moderate: antacids (aluminium hydroxide, calcium carbonate, magnesium oxide), loperamide, aprepitant, clarithromycin, clotrimazole, and several laxatives (bisacodyl, castor oil, polyethylene glycol).
Please refer to the package insert for full safety information, including warnings.
Conclusion and Next Steps
Decision: Hold
Rationale: The only supporting evidence is preclinical macaque data on a virus closely related to HIV, which the drug already treats. There are no registered trials, so this does not represent a new human indication. Other higher-ranked predictions (feline AIDS, rare neurodevelopmental disorder, benign tumours, hyperlipidaemia) have no meaningful supporting evidence either. The HCV co-infection signal (L3) is limited to retrospective liver-stiffness data and drug-interaction work, and does not show anti-HCV activity.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, since the approved indication text and label safety data are not available
- Mechanism of action data from DrugBank
- Clarification of whether a new human indication is actually being sought, or whether the goal is formulation or regimen expansion within HIV (for example long-acting use or pregnancy)
- If so, human clinical evidence beyond the macaque studies
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.